Objective: To analyze density of stromal tumor-infiltrating lymphocytes (sTIL) and expression of lymphocyte-activation gene-3 (LAG-3) protein in advanced gastric adenocarcinomas, and to investigate the correlation of sTIL and LAG-3 with the prognosis in patients with advanced gastric adenocarcinoma. Methods: The clinicopathological characteristics and follow-up data of 260 patients with advanced gastric adenocarcinoma were collected at Fujian Cancer Hospital, from January 2011 to December 2014. The percentage of sTILs was reported semi-quantitatively using histological section evaluation, the LAG-3 protein was detected using immunohistochemistry, and the expression was correlated with the clinicopathological features and patient outcomes. Results: Among the 260 cases, high density of sTIL was detected in 173 cases (66.5%) while LAG-3 high expression was observed in 160 cases (61.5%). These cases were divided into four groups. Group Ⅰ: 48 cases (18.5%) were sTIL low/LAG-3 low; group Ⅱ: 52 cases (20.0%) were sTIL high/LAG-3 low; group Ⅲ: 39 cases (15.0%) were sTIL low/LAG-3 high; group Ⅳ: 121 cases (46.5%) were sTIL high/LAG-3 high. Kaplan-Meier survival analyses showed that patient prognoses were related to age, tumor size, tumor location, Lauren classification, perineural invasion, vascular invasion, TNM staging, postoperative adjuvant chemotherapy and molecular classification (P<0.05). Meanwhile, higher densities of sTIL and higher expression of LAG-3 were associated with better prognosis. Multivariate survival analysis showed age, tumor size, Lauren classification and postoperative adjuvant chemotherapy were independent prognostic factors for patient survival. The results showed a poor prognosis in low-sTIL/low-LAG-3 patients. Conclusions: Compared with low density of sTIL and low expression of LAG-3, high density of sTIL and high expression of LAG-3 are associated with better outcomes in patients with advanced gastric adenocarcinoma, respectively. Combined detecton of sTIL and LAG-3 may be more useful in gastric cancer than using either alone. Age, tumor size, Lauren classification and postoperative adjuvant chemotherapy are independent prognostic factors for patients with advanced gastric adenocarcinoma.
Adenocarcinoma/pathology* ; Humans ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating/metabolism* ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/pathology*

ObjectiveTo investigate the efficacy and mechanism of tetramethylpyrazine derivative T-006 on learning and memory function of APP/PS1/Tau transgenic （3×Tg） mice. MethodsEight-month-old 3×Tg mice and their wild-type （WT） littermates were divided into WT group， WT+T-006 （10 mg/kg） group， 3×Tg group， low-dose T-006 group （1 mg/kg）， medium-dose T-006 group （3 mg/kg）， high-dose T-006 group （10 mg/kg）， donepezil group （1.3 mg/kg） and memantine group （5 mg/kg）. Within 4 months， T-006 and donepezil were continuously administered once a day and memantine twice a day. Behavioral tests including novel object recognition， step-down avoidance and morris water maze were performed to evaluate learning and memory function of mice. Immunohistochemistry was used to observe the deposition of amyloid plaques in the hippocampus of mice. Western blotting was employed to detect the protein expression of APP， BACE-1， PSD95， synapsin I， synapsin Ⅱ， synaptophysin， BDNF， CREB and p-CREB. ResultsT-006 treatment reduced the numbers of errors in the step-down avoidance test （P< 0.05）， significantly reduced the APP expression and increased the expression of PSD95， synaptophysin， synapsin I and BDNF （P<0.05）. ConclusionT-006 improves the learning and memory function of 3×Tg mice and reduces the APP expression， which may be explained by the increase of synaptic associated protein expression.

Aged ; Cognitive Dysfunction/epidemiology* ; Cross-Sectional Studies ; Geriatric Assessment ; Humans ; Independent Living ; Sarcopenia/epidemiology*

Four casssane diterpenes were isolated from the ethanol extract of the seeds of Caesalpinia decapetala (Fabaceae), with a combination of various chromatographic approaches, including silica gel, Sephadex LH-20, reverse phase C₁₈ and so on. On the basis of spectroscopic data analysis, they were identified as caesalpinin MQ (1), neocaesalpin N (2), caesalmin F (3) and α-caesalpin (4). Among them, compound 1 is a new diterpene, compounds 2-4 were isolated for the first time from the plant of C. decapetala.

PrME and NS1 gene were the two main immuneprotect proteins of Japanese encephalitis virus (JEV), and they were also N-linked glycosylation proteins. To clear the effect of N-glycosylation on JEV immunity, the N-glycosylation site of prME and NS1 gene were eliminated by site-directed mutant PCR, subtituting the N to Q. And the the mutant genes were subcloned into eukaryotic expression plasmid. Four-weeks female mice were immuned with the wildtype and mutant gene by twice. The antibodies against prME were detected by ELISA and the neutralization antibodies were tested by viral neutralizing assay. The immunoprotection were determined by attack with JEV virulent strain. Compare with the wild-type gene immuned-groups, one N-glycan eliminated prME gene could induce a little higher ELISA antibody, neutralization antibody and immunoprotection, but the immunity of gene with both N-glycan absence was decreased. The similar status were observed in the wildtype and mutant NS1 groups. Thus these results show that the N-linked glycosylation in the prME and NS1 gene were correlated with the immunity, one glycan absent would enhance the immunity but both two loss would impair it.
Animals ; Antibodies, Viral ; immunology ; Encephalitis Virus, Japanese ; genetics ; immunology ; metabolism ; Encephalitis, Japanese ; immunology ; virology ; Female ; Glycosylation ; Humans ; Mice ; Mice, Inbred BALB C ; Viral Nonstructural Proteins ; genetics ; immunology ; metabolism

Objective To investigate the impact of cytochrome P450 (CYP) 2C19 681G>A polymorphism on long-term prognosis of clopidogrel-treated Chinese patients after percutaneous coronary intervention (PCI).Methods Between January 1, 2009 and August 31,2009, 267 patients with coronary heart disease who received PCI and treated with clopidogrel for 12 months were enrolled. CYP2C19*2 was detected by MALDI-TOF MS and patients were grouped into CYP2C19*1/*1(n=130) and CYP2C19*2 carriers group (n=137). Follow-up was 12 months. The primary endpoint was angina recurrence, urgent coronary revascularization, acute myocardial infarction, stent thrombosis, death and the combined end points. Results Baseline data were similar between two groups (P>0.05).Urgent coronary revascularization and the combined end points occurred more frequently in CYP2C19*2 carriers than in CYP2C19*1/*1 patients (7.3% vs. 1.5% and 8.0% vs. 2.3% respectively,all P<0.05). But incidence of angina recurrence, acute myocardial infarction, stent thrombosis and death was similar between two groups (all P>0.05).Hazard risk of 1 year cumulative survival of CYP2C19*2 carriers group was significantly higher than CYP2C19*1/*1 group after PCI (HR=3.59, 95%CI: 1.02-12.87, P<0.05). Conclusion CYP2C19 681G>A polymorphism is a determinant of prognosis in coronary heart disease patients receiving chronic clopidogrel treatment after PCI.

BACKGROUNDLiver injury is one of the most important adverse effects of antiretroviral therapy, leading to therapy changing or discontinuation. Data on liver injury in human immunodeficiency virus-1-infected patients receiving antiretroviral therapy are limited in China. The purpose of this study was to investigate the features of liver injury in human immunodeficiency virus type 1-infected patients receiving non-nucleosides reverse transcriptase inhibitors-based antiretroviral therapy in China.

METHODSSeventy-five patients on antiretroviral therapy containing non-nucleosides reverse transcriptase inhibitors were retrospectively studied. The patients were divided into 2 groups: group 1 (with liver injury, n = 45) and group 2 (without liver injury, n = 30). The features of liver injury were analyzed. The sex, age, baseline CD4 counts, hepatitis B virus (HBV) and/or hepatitis C virus (HCV) co-infection, hepatotoxic drug use and nevirapine or efavirenz use were compared between two groups.

RESULTSForty-five patients (60.0%), 31 (68.9%) males and 14 (31.1%) females, aged 12 to 52 years (averaged (39 ± 9) years), experienced at least one episode of liver injury. Forty (53.3%) patients were co-infected with HBV and/or HCV, 42 (56%) patients had concomitant use of antituberculosis drugs or cotrimoxazole, 46 (61.3%) and 29 (38.7%) patients received regimen containing nevirapine and efavirenz, respectively. Grade 1 liver injuries were observed in 26 (57.8%) patients, grade 2 in 16 (35.6%), grade 3 in 2 (4.0%) and grade 4 in 1 (2.2%). Three (6.7%) patients discontinued highly active antiretroviral therapy (HAART) due to liver injury. In group 1, there were 29 (64.4%) patients co-infected with HBV and/or HCV, 32 (71.1%) patients received regimen containing nevirapine, and 30 (66.7%) patients had concomitant use of anti-tuberculosis drugs or cotrimoxazole, respectively, significantly higher than those in group 2 (11 (36.7%), 14 (46.7%) and 12 (40%), respectively; P = 0.018, 0.033, 0.023, respectively). The sex, age, baseline CD4 counts and disease stage were not factors associated with liver injury.

CONCLUSIONSLiver injury associated with HAART containing non-nucleosides reverse transcriptase inhibitors was mild to moderate and those who were co-infected with HBV and/or HCV, had concomitant use of antituberculosis drugs or cotrimoxazole and received a regimen containing nevirapine were prone to liver injury while receiving HAART.

Acquired Immunodeficiency Syndrome ; drug therapy ; Adolescent ; Adult ; Antiretroviral Therapy, Highly Active ; adverse effects ; Chemical and Drug Induced Liver Injury ; etiology ; Child ; Female ; HIV-1 ; Humans ; Male ; Middle Aged ; Nevirapine ; adverse effects ; Retrospective Studies ; Reverse Transcriptase Inhibitors ; adverse effects

OBJECTIVETo investigate the feasibility of repairing the wounds in the distal feet with dorsal metatarsal artery distal perforator pedicle link-pattern flaps.

METHODSSince January of 2004 to April of 2009, 30 patients with distal wounds in the feet underwent surgical wound repair using by dorsal metatarsal arteries distal perforator pedicle link-pattern flaps. Seventeen patients used the 1, 2 dorsal metatarsal artery distal perforator flaps, and 13 had the 3, 4 dorsal metatarsal artery distal perforator flaps, with the flaps measuring 4 cmx4 cm to 8 cmx7cm and the flap pedicle ranged 3-6 cm in length. The donor sites were repaired with skin grafting.

RESULTSTwenty-nine flaps survived completely and 1 flap showed partial necrosis in the distant part (2.0 cmx1.0 cm). Twenty-one patients were followed up for an average of 11 months, during which the color, texture, and contour of the flaps remained normal without ulcers in the donor sites or the flaps.

CONCLUSIONThe wounds in the distal feet can be repaired by dorsal metatarsal artery distal perforator pedicle link-pattern flaps, which is a simple, applicable and safe procedure.

Adolescent ; Adult ; Arteries ; surgery ; Female ; Foot ; surgery ; Humans ; Male ; Metatarsal Bones ; blood supply ; Middle Aged ; Perforator Flap ; blood supply ; Reconstructive Surgical Procedures ; methods ; Skin Transplantation ; methods ; Soft Tissue Injuries ; surgery ; Young Adult

Objective To compare the clinical characteristics and clinical outcomes in young (≤45 years) female and male coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI). Methods Angiographic and clinical data from 124 premenopausal female patients who underwent elective PCI from April 2004 to February 2008 were compared to age-matched 430 male patients who underwent elective PCI between 2006 and 2007 in our department. All patients were treated according to guidelines and coronary angiography was repeated after 6 months. One year clinical follow-up were performed in all patients. Results Incidences of dyslipidemia, the history of myocardial infarction and smoking were significantly lower in female patients than in male patients (all P < 0.01 ). Left main, left anterior descending and bifurcation lesions were more common while type C lesion and right coronary lesion were less common in young female CAD group compared to young male CAD group (P <0. 01 -0. 05). The average lesion length in female patients was significantly longer than that in male patients [ (20. 36±13.37)mm vs.( 23.04±13.86) mm, P < 0. 05 ]. The in-hospital and follow-up incidences of major adverse cardiac events,stent thrombosis and in-stent restenosis were similar between young female and male CAD patients.Conclusions CAD risk factors were less and vessel lesions were more likely to be found at left main, left anterior descending and bifurcation in young female CAD patients compared to young male CAD patients.The clinical outcomes were similar between young female and male CAD patients.

OBJECTIVETo investigate the growth inhibition and apoptosis of gastric cancer cell MKN45 induced by oridonin and its mechanism.

METHODSThe MTT method was used to investigate the inhibitory effect of oridonin on MKN45 cells. The AO/EB and Hoechst 33258 staining were used to observe the cell morphologic changes of apoptosis induced by oridonin. Prophase apoptotic ratio and cell cycle change were evaluated by GuavaEasycyte PCA-96 system. The expressions of Bcl-2, Bax and caspase 3 proteins were determined by Western blot.

RESULTSOridonin significantly inhibited the proliferation of MKN45 cells in dose- and time-dependent manner. Typical apoptotic features of the cells treated with oridonin were found by AO/EB and Hoechest33258 staining. When MKN45 cells were treated with different doses of oridonin for 12 h, the prophase apoptotic ratio was stepped up from 3.3% (untreated group) to 8.7%-17.9%; after 24 h, from 4.8% (untreated group) to 13.9%-29.3%. There was significant difference between treated and untreated groups (P <0.01). After treatment with oridonin for 24 h, MKN45 cells were arrested at G(2)/M phase. Western blot analysis showed up-regulated expression of Bax and caspase-3, and no significant change of Bcl-2, but Bcl-2/Bax ratio decreased significantly.

CONCLUSIONSOridonin significantly inhibits the proliferation of MKN45 cell. Apoptosis of MKN45 induced by oridonin may be associated with the up-regulated expression of Bax and the change of Bcl-2/Bax ratio, thus to activate the caspase pathway.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Diterpenes, Kaurane ; pharmacology ; Humans ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Stomach Neoplasms ; metabolism ; bcl-2-Associated X Protein ; metabolism